In 430 B.C., a new and deadly disease — its cause remains
a mystery — swept into Athens. The walled Greek city-state
was teeming with citizens, soldiers and refugees of the war then
raging between Athens and Sparta. As streets filled with corpses,
social order broke down. Over the next three years, the illness
returned twice and Athens lost a third of its population. It lost
the war too. The Plague of Athens marked the beginning of the end
of the Golden Age of Greece.

The Plague of Athens is one of 10 historically notable outbreaks
described in an article in The Lancet Infectious Diseases by
authors from the National Institute of Allergy and Infectious Diseases
(NIAID), part of the National Institutes of Health. The phenomenon
of widespread, socially disruptive disease outbreaks has a long
history prior to HIV/AIDS, severe acute respiratory syndrome (SARS),
H5N1 avian influenza and other emerging diseases of the modern
era, note the authors.

"There appear to be common determinants of disease emergence
that transcend time, place and human progress," says NIAID
Director Anthony S. Fauci, M.D., one of the study authors. For
example, international trade and troop movement during wartime
played a role in both the emergence of the Plague of Athens as
well as in the spread of influenza during the pandemic of 1918-19.
Other factors underlying many instances of emergent diseases are
poverty, lack of political will, and changes in climate, ecosystems
and land use, the authors contend. "A better understanding
of these determinants is essential for our preparedness for the
next emerging or re-emerging disease that will inevitably confront
us," says Dr. Fauci.

"The art of predicting disease emergence is not well developed," says
David Morens, M.D., another NIAID author. "We know, however,
that the mixture of determinants is becoming ever more complex,
and out of this increased complexity comes increased opportunity
for diseases to reach epidemic proportions quickly."

For example, more people travel more often over greater distances
and in less time now than at any time in the past. One consequence
of the increased mobility in the modern age can be seen in the
2003 outbreak of the novel illness SARS, which rapidly spread from
Hong Kong to Toronto and elsewhere as infected passengers traveled
by air.

To better understand and predict disease emergence, Dr. Morens
and his coauthors stress the need for research aimed at broadly
understanding infectious diseases as well as specifically understanding
how disease-causing microorganisms make the jump from animals to
humans.

In a narrow sense, epidemics are caused by particular microorganisms,
and the study of infectious disease has historically been microbe-focused.
For example, the Black Death (bubonic plague), which killed some
34 million Europeans in the middle of the 14th century,
was caused by the bacterium Yersinia pestis. In a broader
sense, however, epidemics are caused by complex and not fully predictable
interactions between the disease-causing microbe, the human host
and multiple environmental factors, the authors note. The Black
Death, for instance, was borne westward along newly established
land and sea trade routes from its probable origin, China, into
multiple European countries. Similarly, patterns of human movement
along trade routes, specifically truck routes throughout Africa,
played a role in the spread of HIV throughout that continent. Greater
consideration must be given, say the NIAID authors, to broader,
interlinked factors such as climate, urbanization, increased international
travel and the rise of drug-resistant microbes, and the ways in
which these factors combine to spark new epidemics.

Aside from commerce and travel, the NIAID authors point to several
other factors that underlie many notable emerging diseases: poverty,
the breakdown of public hygiene practices, and susceptibility of
human populations to microbes against which they have no pre-existing
immunity. This last factor played a key role in the smallpox epidemic
that afflicted the Aztecs of 16th century Mexico. Smallpox
had ravaged European communities for centuries, but until the Spanish
arrived on the Yucatan coast in 1519, the disease was unknown in
the New World. Historians believe that some 3.5 million people
in central Mexico died in the first year of the epidemic.

Epidemics also can spur advances in public health, note the authors.
They point to the yellow fever epidemics of 1793-98, which began
in the then-U.S. capital, Philadelphia. Though the entire federal
government and most Philadelphians fled, those who remained formed
an emergency government and mobilized such marginalized groups
as African-Americans and immigrants to fight the outbreak. In 1798,
Congress established the Marine Hospital System — forerunner
of the modern U.S. Public Health Service — to provide, at
public expense, medical care for sick and injured merchant seamen.
Historians generally agree that a prime impetus for creating the
Marine Hospital System was the yellow fever epidemics.

Modern epidemiology began in reaction to another epidemic, says
Dr. Morens. In the early 1830s, as cholera made its way along waterways
from Asia towards Europe, French officials attempted to prepare
their country in advance of an outbreak. Teams of scientists were
sent to Poland and Russia to observe the outbreaks there. Throughout
France, coastal health agencies and new quarantine stations were
established; in Paris, a network of health inspection offices was
created to coordinate inspection of wells, cesspools and latrines
of both public and private buildings. Despite these efforts, cholera
arrived in Paris on March 29, 1832, with explosive effect — within
two weeks, there were 1,000 cases, 85 percent of them fatal. Daily
newspapers published lists of cases allowing armchair epidemiologists
to see trends in illness and deaths. "For the first time in
history," write the NIAID authors, "a large-scale emerging
epidemic was scientifically investigated in 'real time' using census
data in a prospective population-based approach that featured analyses
of morbidity and mortality stratified by age-group, sex, occupation,
socioeconomic status and location."

NIAID conducts and supports research — at NIH, throughout
the United States, and worldwide — to study the causes of
infectious and immune-mediated diseases, and to develop better
means of preventing, diagnosing and treating these illnesses. News
releases, fact sheets and other NIAID-related materials are available
on the NIAID Web site at http://www.niaid.nih.gov.

The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.